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Journal of dermatological science2008; 51(2); 103-112; doi: 10.1016/j.jdermsci.2008.03.008

Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair.

Abstract: Wounds on horse limbs can develop exuberant granulation tissue which resembles the human keloid. Clues gained from the study of over-scarring in horses might help control fibro-proliferative disorders. Objective: The aim of the present study was to clone full-length equine ANXA2 cDNA then to study spatio-temporal expression of ANXA2 and MMP1 mRNA and protein, potential contributors to remodeling, during repair of body (normal) and limb (fibro-proliferative) wounds in an established horse wound model. Methods: Cloning of ANXA2 was achieved by screening size-selected cDNA libraries. Expression was studied in intact skin and in biopsies of 1, 2, 3, 4 and 6-week-old wounds of the body and limb. Temporal gene expression was determined by semi-quantitative RT-PCR while protein expression was mapped immunohistochemically. Results: ANXA2 mRNA was up-regulated only in body wounds, corroborating the superior and prompt tissue turnover at this location. Immunohistochemistry partially substantiated the mRNA data in that increased staining for ANXA2 protein was detected in neo-epidermis which formed more rapidly and completely in body wounds. MMP1 mRNA levels in body wounds significantly surpassed those of limb wounds in week one biopsies. The protein was abundant in migrating epithelium of limb wounds at weeks two and four; conversely, body wounds in which epithelialization was near complete showed diminished staining of MMP1. Conclusions: We conclude that ANXA2 and MMP1 might participate in remodeling during wound healing in the horse, and that differences in expression may contribute to the excessive proliferative response seen in the limb.
Publication Date: 2008-04-22 PubMed ID: 18434095DOI: 10.1016/j.jdermsci.2008.03.008Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study focuses on understanding the healing process of normal and pathological wounds in horses and how certain proteins might influence wound repair. This could potentially shed light on the treatment of excessive scarring disorders in humans.

Objective

The research set out to clone the full-length equine ANXA2 cDNA then to study the spatio-temporal expression of ANXA2 and MMP1 mRNA and proteins. These are potential contributors to the wound repair process. The study compared the repair of normal wounds on the body of horses to fibro-proliferative wounds on horse limbs.

Methods

  • The cloning of ANXA2 was achieved by screening size-selected cDNA libraries.
  • Expressions of ANXA2 and MMP1 were studied in intact skin and in wound biopsies taken at 1, 2, 3, 4, and 6-week intervals.
  • Temporal gene expression was determined using semi-quantitative RT-PCR whereas protein expression was mapped immunohistochemically.

Results

The study found that:

  • ANXA2 mRNA was up-regulated only in normal body wounds, indicating a superior and prompt tissue turnover at these locations.
  • The increase of ANXA2 protein was detected more in the new skin layer in body wounds. This implied that fast and fully-formed wound repair happens more in body wounds.
  • MMP1 mRNA levels in normal body wounds were significantly higher than those in fibro-proliferative limb wounds in week one biopsies.
  • MMP1 protein was more abundant in the healing epithelium of limb wounds at weeks two and four. Conversely, body wounds nearing complete healing showed reduced staining of MMP1.

Conclusion

The study concluded that the ANXA2 and MMP1 proteins might have a role in remodeling during the healing process of horse wounds. Moreover, there are differences in the expression of these proteins in normal body wounds and fibro-proliferative limb wounds. These distinct expression patterns may contribute to the excessive proliferative response seen in limb wounds.

Cite This Article

APA
Miragliotta V, Lefebvre-Lavoie J, Lussier JG, Theoret CL. (2008). Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair. J Dermatol Sci, 51(2), 103-112. https://doi.org/10.1016/j.jdermsci.2008.03.008

Publication

ISSN: 0923-1811
NlmUniqueID: 9011485
Country: Netherlands
Language: English
Volume: 51
Issue: 2
Pages: 103-112

Researcher Affiliations

Miragliotta, Vincenzo
  • Department of Veterinary Anatomy, Biochemistry and Physiology, University of Pisa, Viale delle Piagge 2, 56100 Pisa, Italy.
Lefebvre-Lavoie, Josiane
    Lussier, Jacques G
      Theoret, Christine L

        MeSH Terms

        • Animals
        • Annexin A2 / genetics
        • Annexin A2 / metabolism
        • Biopsy
        • Cell Proliferation
        • DNA, Complementary / genetics
        • Female
        • Gene Expression Regulation
        • Horses
        • Matrix Metalloproteinase 1 / genetics
        • Matrix Metalloproteinase 1 / metabolism
        • Models, Animal
        • RNA, Messenger / metabolism
        • Skin / cytology
        • Skin / metabolism
        • Skin / pathology
        • Wound Healing / physiology
        • Wounds and Injuries / metabolism
        • Wounds and Injuries / pathology

        Citations

        This article has been cited 3 times.
        1. Sun Q, Yu ET, Zhou Y, Tong S, Zhou KJ, Guo S. Individualized surgery combined with radiotherapy and triamcinolone acetonide injection for the treatment of auricular keloids. BMC Surg 2021 May 22;21(1):256.
          doi: 10.1186/s12893-021-01253-9pubmed: 34022880google scholar: lookup
        2. Sun Q, Guo S, Wang CC, Sun X, Wang D, Xu N, Jin SF, Li KZ. Cross-talk between TGF-β/Smad pathway and Wnt/β-catenin pathway in pathological scar formation. Int J Clin Exp Pathol 2015;8(6):7631-9.
          pubmed: 26261683
        3. Mosseri S, Hetzel U, Hahn S, Michaloupoulou E, Sallabank HC, Knottenbelt DC, Kipar A. Equine sarcoid: In situ demonstration of matrix metalloproteinase expression. Vet J 2014 Nov;202(2):279-85.
          doi: 10.1016/j.tvjl.2014.07.026pubmed: 25439440google scholar: lookup